The enzyme guanylate cyclase forms cyclic GMP from GTP. It occurs in high activity in lung in two forms, soluble and insoluble. We have been studying the relationship between the two forms. Solubilization of the insoluble enzyme with nonionic detergents converts it to a form which is nonsedimentible by centrifugation, but is still much larger than the naturally soluble enzyme. We will attempt to reduce the molecular weight of the solubilized enzyme by treatment with other detergents, and with other enzymes. We have found that the activity of the soluble enzyme can be increased four fold, by an oxygen dependent reaction. This reaction appears to require a low concentration of copper ions. We will determine the sequence of events in the activation, and the molecular changes in the enzyme. BIBLIOGRAPHIC REFERENCES: White, A.A. and Lad. P.J. "Activation of the Soluble Guanylate Cyclase from Rat Lung by Preincubation". Fed. Proc. 34:232 (1975). White, A.A. and Lad, P.J. "Differential Effects of Detergents Upon the Soluble and Particulate Guanylate Cyclases from Rat Lung." Fed. Proc. 35:1731 (1976).